Project Summary: Ischemic heart disease can lead to myocardial infarction (MI), a major cause of morbidity and mortality worldwide. After MI scar forms in the affected region, the heart dilates, and cardiac function is depressed and can lead to heart failure. Current therapies do not reverse or reduce the death of tissue caused by MI. Cell therapy could be a new strategy to treat post MI remodeling, but to date has been largely ineffective. We have recently identified a novel stem cell that resides deep within the bone stroma, which we term Cortical Bone Stem Cells (CBSCs). We have shown, in a mouse MI model, that CBSCs reduce scar size and enhance cardiac function after MI. These beneficial effects appear to be mediated by paracrine mechanisms that we have shown can be cardioprotective, angiogenic, and immune modulatory. The proposed research is the next step in determining if these cells might be useful to treat patients who have suffered an MI. The Aims of this research are to determine the best CBSC dose, route and time of delivery to induce more effective cardiac repair in a swine MI model. We will also determine if CBSCs improve post MI remodeling by cardioprotective, angiogenic, cardiogenic and/or immune modulatory effects. Our proposed study should provide novel insights into how to use cell therapy to improve cardiac structure and function after MI.